Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001195248.2(APTX):c.1003C>T(p.His335Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
APTX (HGNC:15984): (aprataxin) This gene encodes a member of the histidine triad (HIT) superfamily. The encoded protein may play a role in single-stranded DNA repair through its nucleotide-binding activity and its diadenosine polyphosphate hydrolase activity. Mutations in this gene have been associated with ataxia-ocular apraxia. Alternatively spliced transcript variants have been identified for this gene.[provided by RefSeq, Aug 2010]
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Dec 07, 2022
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The APTX c.1003C>T (p.His335Tyr) missense variant results in the substitution of histidine at amino acid position 335 with tyrosine. To our knowledge, this variant has not been reported in the peer-reviewed literature. This variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. The c.1003C>T variant lies within the ZNF domain, thought to be important in substrate specificity with His335 as one of four zinc binding residues (PMID: 25637650). Multiple lines of computational evidence suggest the variant may have a deleterious effect on the gene or gene product. Based on the available evidence, the c.1003C>T (p.His335Tyr) variant is classified as a variant of uncertain significance for ataxia with oculomotor apraxia. -